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Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia

Philadelphia chromosome-like B-lymphoblastic leukemia (Ph-like ALL) describes a group of genetically heterogeneous, Ph-negative entities with high relapse rates and poor prognoses. A Janus-kinase-2 (JAK2) rearrangement has been reported in approximately 7% of Ph-like ALL patients whose therapeutic r...

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Autores principales: Zhang, Xin-Yue, Dai, Hai-Ping, Li, Zheng, Yin, Jia, Lang, Xing-Ping, Yang, Chun-Xiao, Xiao, Sheng, Zhu, Ming-Qing, Liu, Dan-Dan, Liu, Hong, Shen, Hong-Jie, Wu, De-Pei, Tang, Xiao-Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831028/
https://www.ncbi.nlm.nih.gov/pubmed/33505919
http://dx.doi.org/10.3389/fonc.2020.611467
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author Zhang, Xin-Yue
Dai, Hai-Ping
Li, Zheng
Yin, Jia
Lang, Xing-Ping
Yang, Chun-Xiao
Xiao, Sheng
Zhu, Ming-Qing
Liu, Dan-Dan
Liu, Hong
Shen, Hong-Jie
Wu, De-Pei
Tang, Xiao-Wen
author_facet Zhang, Xin-Yue
Dai, Hai-Ping
Li, Zheng
Yin, Jia
Lang, Xing-Ping
Yang, Chun-Xiao
Xiao, Sheng
Zhu, Ming-Qing
Liu, Dan-Dan
Liu, Hong
Shen, Hong-Jie
Wu, De-Pei
Tang, Xiao-Wen
author_sort Zhang, Xin-Yue
collection PubMed
description Philadelphia chromosome-like B-lymphoblastic leukemia (Ph-like ALL) describes a group of genetically heterogeneous, Ph-negative entities with high relapse rates and poor prognoses. A Janus-kinase-2 (JAK2) rearrangement has been reported in approximately 7% of Ph-like ALL patients whose therapeutic responses to JAK inhibitors have been studied in clinical trials. Here, we report a novel STRBP-JAK2 fusion gene in a 21-year-old woman with Ph-like ALL. Although a normal karyotype was observed, a hitherto unreported JAK2 rearrangement was detected cytogenetically. STRBP-JAK2 fusion was identified by RNA sequencing and validated by Sanger sequencing. The Ph-like ALL proved refractory to traditional induction chemotherapy combined with ruxolitinib. The patient consented to infusion of autologous chimeric antigen receptor (CAR) T cells against both CD19 and CD22, which induced morphologic remission. Haplo-identical stem cell transplantation was then performed; however, she suffered relapse at just one month after transplantation. The patient subsequently received donor lymphocyte infusion after which she achieved and maintained a minimal residual disease negative remission. However, she succumbed to grade IV graft-versus-host disease 7 months post-transplant. In conclusion, this report describes a novel STRBP-JAK2 gene fusion in a Ph-like ALL patient with a very aggressive disease course, which proved resistant to chemotherapy combined with ruxolitinib but sensitive to immunotherapy. Our study suggests that CAR T-cell therapy may be a viable option for this type of leukemia.
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spelling pubmed-78310282021-01-26 Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia Zhang, Xin-Yue Dai, Hai-Ping Li, Zheng Yin, Jia Lang, Xing-Ping Yang, Chun-Xiao Xiao, Sheng Zhu, Ming-Qing Liu, Dan-Dan Liu, Hong Shen, Hong-Jie Wu, De-Pei Tang, Xiao-Wen Front Oncol Oncology Philadelphia chromosome-like B-lymphoblastic leukemia (Ph-like ALL) describes a group of genetically heterogeneous, Ph-negative entities with high relapse rates and poor prognoses. A Janus-kinase-2 (JAK2) rearrangement has been reported in approximately 7% of Ph-like ALL patients whose therapeutic responses to JAK inhibitors have been studied in clinical trials. Here, we report a novel STRBP-JAK2 fusion gene in a 21-year-old woman with Ph-like ALL. Although a normal karyotype was observed, a hitherto unreported JAK2 rearrangement was detected cytogenetically. STRBP-JAK2 fusion was identified by RNA sequencing and validated by Sanger sequencing. The Ph-like ALL proved refractory to traditional induction chemotherapy combined with ruxolitinib. The patient consented to infusion of autologous chimeric antigen receptor (CAR) T cells against both CD19 and CD22, which induced morphologic remission. Haplo-identical stem cell transplantation was then performed; however, she suffered relapse at just one month after transplantation. The patient subsequently received donor lymphocyte infusion after which she achieved and maintained a minimal residual disease negative remission. However, she succumbed to grade IV graft-versus-host disease 7 months post-transplant. In conclusion, this report describes a novel STRBP-JAK2 gene fusion in a Ph-like ALL patient with a very aggressive disease course, which proved resistant to chemotherapy combined with ruxolitinib but sensitive to immunotherapy. Our study suggests that CAR T-cell therapy may be a viable option for this type of leukemia. Frontiers Media S.A. 2021-01-11 /pmc/articles/PMC7831028/ /pubmed/33505919 http://dx.doi.org/10.3389/fonc.2020.611467 Text en Copyright © 2021 Zhang, Dai, Li, Yin, Lang, Yang, Xiao, Zhu, Liu, Liu, Shen, Wu and Tang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Zhang, Xin-Yue
Dai, Hai-Ping
Li, Zheng
Yin, Jia
Lang, Xing-Ping
Yang, Chun-Xiao
Xiao, Sheng
Zhu, Ming-Qing
Liu, Dan-Dan
Liu, Hong
Shen, Hong-Jie
Wu, De-Pei
Tang, Xiao-Wen
Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia
title Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia
title_full Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia
title_fullStr Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia
title_full_unstemmed Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia
title_short Identification of STRBP as a Novel JAK2 Fusion Partner Gene in a Young Adult With Philadelphia Chromosome-Like B-Lymphoblastic Leukemia
title_sort identification of strbp as a novel jak2 fusion partner gene in a young adult with philadelphia chromosome-like b-lymphoblastic leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831028/
https://www.ncbi.nlm.nih.gov/pubmed/33505919
http://dx.doi.org/10.3389/fonc.2020.611467
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